降钙素基因相关肽对阿霉素心肌细胞毒性的保护作用

目的观察降钙素基因相关肽（ＣＧＲＰ）对阿霉素所致心肌细胞毒性作用的影响。方法采用原代培养乳鼠心肌细胞，以１０－６ｍｏｌＬ－１阿霉素造成急性心肌细胞毒性模型，ＣＧＲＰ作用浓度为１０－８ｍｏｌＬ－１。测定培养基中ＬＤＨ活性及心肌细胞内丙二醛（ＭＤＡ）、钙含量。透射电镜观察心肌细胞超微结构改变。结果阿霉素引起心肌细胞ＬＤＨ漏出明显增加；细胞内ＭＤＡ、钙含量水平明显升高；心肌细胞线粒体明显肿胀、嵴排列不整齐、断裂或消失，肌浆网明显扩张，染色质凝集。阿霉素所致心肌细胞ＬＤＨ漏出与细胞内ＭＤＡ含量水平呈正相关。ＣＧＲＰ可明显减轻阿霉素所致心肌细胞ＬＤＨ漏出及细胞内ＭＤＡ、钙的蓄积，明显减轻心肌细胞超微结构的改变。结论ＣＧＲＰ通过抑制脂质过氧化反应和减轻细胞内钙超载对阿霉素心肌细胞毒性具有保护作用

The protective role of calcitonin gene related peptide againstadriamycin induced acute cadiotoxicity in cultured myocardial cells

AIM To determine the effects of calcitonin gene related peptide (CGRP) against adriamycin induced acute cardiotoxicity on primary cultured myocardial cells. METHODS Primary cultured myocardial cells were treated with 10-6 mol·L-1 adriamycin and 10-6 mol·L-1 adriamycin+10-8 mol·L-1 CGRP. LDH activity in medium, malondialdehyde (MDA) and calcium contents of myocardial cells were assayed. The changes of myocardial cell ultrastructure were observed. RESULTS LDH activity, calcium and MDA contents were significantly increased in adriamycin group compared with that in control group. There was a positive correlation between LDH activity and MDA content. The ultrastructure of myocardial cells showed that the mitochondria were swollen and the sarcoplasmic reticulums expanded. Meanwhile, in adriamycin+CGRP group, CGRP might significantly reduce the leakage of LDH from myocardial cells, and lessen the increase in calcium and MDA contents. The ultastructure damage was also significantly improved. CONCLUSION It is suggested that CGRP can significantly reduce adriamycin induced cardiotoxicity on myocardial cells by inhibiting lipid peroxidation and attenuating calcium overload.